Sought FUS, Found TAF—A New Fibril in Frontotemporal Dementia
Cryo-EM identified TAF15 filaments at the heart of protein aggregates in some FTD cases. Should FDT-FUS be renamed FTD-FET?
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Mouse Model LOADs on the Risk Factors
When LOAD2 mice, which carry Alzheimer’s risk variants, eat a fatty diet, their proteomes change, their neurons die, and their memories fail. All sans amyloid plaques.
Cholesterol Metabolite Ups Estrogen Signaling to Keep Females Sharp
The enzyme cholesterol 24-hydroxylase protected against cognitive decline and tau pathology—but only in females.
Major Histocompatibility Complex Curbs AD/PD Risk; Shows Tau to T Cells
Certain MHC class II subtypes reduce a person’s risk of Alzheimer's and Parkinson's. They bind an acetylated snippet of tau.
In Lipoparticles, ApoE Double Belt Keeps the Fat In
The α-helical chains of two ApoEs wrap around lipoprotein discs. They circle in opposite directions.
Posterior Cortical Atrophy Is a Form of Young-Onset Alzheimer’s
Among 1,092 people with PCA, symptoms started around age 60, and 94 percent had amyloid plaques or neurofibrillary tangles.
Goodbye, APOE4. Hello, Healthy Brain?
Two men with loss-of-function variants in their APOE4 alleles escaped amyloid pathology. One was in his 90s.
Under the Radar: APP Uppsala Fibrils Evade Microglia, PiB, Leqembi
In mice, these Aβ fibrils avoid riling microglia and astrocytes. They also evade both PiB and lecanemab.
From St. Louis to Beijing: AD Biomarkers Change Similarly Before Symptoms
Using different methods and studying different populations, two studies report similar trajectories of fluid and imaging biomarkers over a 20-year span of AD.
Does Synchronizing Brain Waves Bring Harmony?
In early stage trials, light and sound promoted neuronal communication, calmed immune cells, and slowed brain atrophy, but cognitive benefit remains unclear.
Neuroprotective Extracellular Matrix Seen in C9ORF72 ALS/FTD Models
Modeling physiological dipeptide repeat expression and partial loss of normal C9ORF72 protein, new knock-in mice show a TGF-β1-driven collagen response in their spinal neurons.
TREM1 Muddles Myeloid Cell Metabolism and Memory in Old Mice
In peripheral macrophages and microglia, the receptor disrupts glucose metabolism. TREM1-deficient amyloidosis mice also had healthier neurons, better memories.
Yeast Chaperone Melts Protein Aggregates
Scientists have turned a yeast heat shock protein into a powerful disaggregase that attacks TDP-43, FUS, and α-synuclein mutants.
Aβ 'Receptors' Retard Fibrillization, Enhancing Toxicity
By interfering with Aβ fibril growth, prion and two other cell-surface proteins may drive production of smaller, more toxic, oligomers and protofibrils.
Could Sumoylation Take Down Tangles?
The addition of SUMO2 to tau prevents its phosphorylation and aggregation, preserving synapses and memory in tauopathy mouse models.
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